Cystic Fibrosis (CF) is one of the most common, life limiting autosomal recessive genetic disease in the U.S., with a prevalence of about 30.000 total patients. Cystic Fibrosis has no cure and incurs a huge lifetime financial burden. At least one person with CF dies each day. The average annual cost of CF care per individual with private healthcare insurance in 2006 was $48,098, more than 22 times the cost of an individual without CF. Mortality in CF patients is mostly due to progressive respiratory failure from irreversible obstructive lung disease. The lung is destroyed by infection and complicated by an intrinsically pro-inflammatory NFKB- mediated neutrophil-dominated state in the airway. Airways are infiltrated with increased numbers of neutrophils that are attracted by Il-8. The major source of IL-8 in the CF airway is the airway epithelium, and the resulting high levels of IL-8 attract a large influx of neutrophils and other inflammatory cells. The CF epithelial cells also secrete high levels of other proinflammatory cytokines, but they are in less abundance. IL-8 hypersecretion in the CF lung is due to a dysfunctional TNFa/NFB signaling pathway. For that reason an attractive pharmaceutical strategy has been to find a drug that would suppress that part of the pathway involved in IL-8 expression, but not other parts required for physiological responses to infection. This project was devised when low concentrations of the drug digitoxin were discovered to suppress IL-8 hypersecretion by CF lung epithelial cells. The mechanism of digitoxin action is to suppress the TNFa/NFB signaling pathway. Digitoxin specifically blocks the interaction between the TNF Receptor and the adaptor protein TRADD. This site of interaction is known as the initiator for assembly of a set of three other adaptor proteins, the inflammasome which leads downstream to IL-8 expression. The oral bioavailability of digitoxin is approximately 100%, and therefore we hypothesize that digitoxin will safely suppress IL-8 dependent lung inflammation in cystic fibrosis patients. The purpose of this proposal is to complete the third and final cohort of CF patients to test this hypothesis and select the minimum safe and effective dose. Primary Objective: To measure the effects of digitoxin on IL-8 and neutrophil counts in induced sputum in stable CF patients. The study is a randomized, double blind, placebo-controlled, repeat dosing trial evaluating the effects of 28 days of digitoxin on IL-8 and neutrophil concentrations in induced sputum in CF subjects with mild to moderate cystic fibrosis lung disease. Three groups of 8 subjects each will be given either 0.05 mg or 0.10 mg digitoxin or a placebo. Twenty-four total patients are planned for the study. Secondary Objective 1: To measure the pharmacokinetics of digitoxin in serum in stable CF patients. The length of study participation for each subject is 70 days, and is defined as Screening Days (week ); -4 to day -2) Treatment Days (Day 1-28); and Recovery Days (Day 28-42). Serum (pharmacokinetics) is collected at intervals for analysis. Secondary Objective 2: To measure safety indices, including ECG changes and sputum microbiology, in stable CF patients. Secondary Objective 3: To measure the effect of digitoxin on gene expression in nasal epithelial cells of stable CF patients. Nasal epithelial cells are collected on Day 0 prior to study drug dosing and on day 28 after last study dose. Secondary Objective 4: To measure quality of life scores using the CFQ-R.